The mouse CD1d-restricted repertoire is dominated by a few autoreactive T cell receptor families

Se Ho Park, Angela Weiss, Kamel Benlagha, Tim Kyin, Luc Teyton, Albert Bendelac

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

To define the phenotype and T cell receptor (TCR) repertoire of CD1d-dependent T cells, we compared the populations of T cells that persisted in major histocompatibility complex (MHC)-deficient mice, which lack mainstream T cells, with those from MHC/CD1d doubly deficient mice, which lack both mainstream and CD1d-dependent T cells. Surprisingly, up to 80% of the CD1d-dependent T cells were stained by tetramers of CD1d/α-galactosylceramide, which specifically identify the previously described CD1d autoreactive Vα14-Jα18/Vβ38 natural killer (NK) T cells. Furthermore, zooming in on the CD1d-dependent non-Vα14 T cells, we found that, like Vα14 NK T cells, they mainly expressed recurrent, CD1d autoreactive TCR families and had a natural memory phenotype. Thus, CD1d-restricted T cells differ profoundly from MHC-peptide-specific T cells by their predominant use of autoreactive and semiinvariant, rather than naive and diverse, TCRs. They more closely resemble other lineages of innate lymphocytes such as B-1 B cells, γδ T cells, and NK cells, which express invariant or semiinvariant autoreactive receptors. Finally, we demonstrate that the MHC-restricted TCR repertoire is essentially non-cross-reactive to CD1d. Altogether, these findings imply that lipid recognition by CD1d-restricted T cells may have largely evolved as an innate rather than an adaptive arm of the mouse immune system.

Original languageEnglish
Pages (from-to)893-904
Number of pages12
JournalJournal of Experimental Medicine
Volume193
Issue number8
DOIs
Publication statusPublished - 2001 Apr 16

Keywords

  • Autoreactivity
  • CD1
  • Lipid antigens
  • T cell development
  • TCR

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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